Mechanisms and molecular probes of sirtuins.
Sirtuins are critical regulators of many cellular processes, including insulin secretion, the cell cycle, and apoptosis. Sirtuins are associated with a variety of age-associated diseases such as type II diabetes, obesity, and Alzheimer's disease. A thorough understanding of sirtuin chemical mechanisms will aid toward developing novel therapeutics that regulate metabolic disorders and combat associated diseases. In this review, we discuss the unique deacetylase mechanism of sirtuins and how this information might be employed to develop inhibitors and other molecular probes for therapeutic and basic research applications. We also cover physiological regulation of sirtuin activity and how these modes of regulation may be exploited to manipulate sirtuin activity in live cells. Development of molecular probes and drugs that specifically target sirtuins will further understanding of sirtuin biology and potentially afford new treatments of several human diseases.
Smith
Brian C
BC
Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison, WI 53706, USA.
Hallows
William C
WC
Denu
John M
JM
D000107:Acetylation; D000818:Animals; D015415:Biomarkers; D051548:Histone Acetyltransferases / Q000378:metabolism; D006801:Humans; D015335:Molecular Probes / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D037761:Sirtuins / Q000378:metabolism*
D015415:Biomarkers; D015335:Molecular Probes; D009243:NAD; D051548:Histone Acetyltransferases; D037761:Sirtuins